One of the primary problems facing researchers and clinicians in the broad field of tissue engineering and regenerative medicine is the fabrication of biomaterial substrates that provide appropriate three-dimensional architecture, mechanical support, and the ability to deliver both cells and growth factors tailored to a specific tissue of interest. In situ gel formation is a concept of great interest for tissue engineers as it enables the delivery of a hydrogel matrix encapsulating cells and growth factors to defects of any shape using minimally invasive surgical techniques.
Smart polymers, polymeric materials that respond to environmental stimuli, have become attractive materials in biotechnology and medicine. In response to small changes in the environment, such polymers undergo strong conformational changes that result in rapid desolvation of the polymer molecules and phase separation of the solution. Functional groups have been identified and polymers synthesized that respond to a variety of stimuli, including changes in temperature, pH, osmotic pressure, ionic strength, pressure, and electric or magnetic field. Temperature-sensitive hydrogel-forming polymers are one of the most common among these materials and have been previously studied as temperature-regulated drug delivery systems and have also been investigated as matrices for injectable tissue engineering applications. In situ gel formation is a concept of great interest for tissue engineers as it enables the delivery of a hydrogel matrix encapsulating cells and/or growth factors to defects of any shape using minimally invasive surgical techniques. Various natural and synthetic polymers have been modified chemically with moieties for chemical crosslinking, including acrylic esters, methacrylic esters, cinnamoyl esters, fumaric esters, and vinyl sulfone, to yield injectable biodegradable matrices. In situ gel formation by radical polymerization of the electron-poor olefins can be induced photochemically or thermally without harming encapsulated cells. However, only low concentrations of radical initiators and crosslinking agents are tolerated by encapsulated cells in thermally induced crosslinking reactions, and thus, certain important parameters such as gelation kinetics, crosslinking densities, and resulting mechanical properties of the hydrogels can only be varied to a limited extent without compromising the cytocompatibility of the process. Photocrosslinking, on the other hand, requires accessibility of the defect for a light source and hydrogel dimensions are limited to ensure homogenous polymerization. Irradiation times and doses also have to be carefully controlled to avoid detrimental effects of the curing light on cells or tissues.
During the fabrication of hydrogels or polymer networks by chemical crosslinking, certain important parameters such as gelation kinetics, crosslinking densities and resulting mechanical properties of the hydrogels can only be varied to a limited extent without compromising the cytocompatibility of the process. Cytocompatible chemical gelation methods, for instance, typically yield firm hydrogels after several minutes, while thermally induced gelation of thermo-sensitive polymer solutions occurs almost instantaneously once a certain temperature is reached.